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Osteoarthritis (OA) is a painful, progressive chronic inflammatory disease marked by cartilage destruction. Certain synovial inflammatory cytokines, such as IL-1β and TNF-α, promote OA inflammation and pain. <i>Lactobacillus</i> spp. is a well-known probiotic with anti-inflammatory, analgesic, antioxidant, and antiosteoporotic properties. This study evaluated the therapeutic effects of a live <i>L. plantarum</i> strain (GKD7) in the anterior cruciate ligament transection (ACLT)-induced OA rat model. The results show that oral administration of live <i>L. plantarum</i> GKD7 improved weight-bearing asymmetry after ACLT surgery. Moreover, micro-computed tomography images and histopathological analysis show that oral live <i>L. plantarum</i> GKD7 improved subchondral bone architecture, protected articular cartilage against ACLT-induced damage, and reduced synovial inflammation. <i>L. plantarum</i> GKD7 also reduced IL-1β and TNF-α production in OA cartilage and synovium. Thus, orally administered live <i>L. plantarum</i> GKD7 appears to effectively slow the progression of OA.